Calmodulin is a small, Ca2+-dependent regulatory protein that activates at least nine distinct enzyme activities important to the overall cell's metabolism. This protein besides binding Ca2+ and the activated enzymes, also binds phenothiazine drugs in a calcium-dependent manner and this binding prevents enzyme activation by calmodulin. I propose to locate within the known calmodulin amino acid sequence those regions that form the Ca2+-binding, enzyme-binding, and drug-binding domains of this important regulatory protein. I also propose to isolate the calmodulin-binding domains from several of the enzymes activated by calmodulin and to characterize these. Finally, it has been proposed that calmodulin serves as a central receptor protein that mediates the second-messenger effects of Ca2+ in stimulus-response coupling. I propose to test the feasibility of this theory utilizing transient kinetics and to further characterize the steady-state kinetics of calmodulin regulation of Ca2+-homeostasis via its regulation of erythrocyte Ca2+-transport ATPase, and cyclic nucleotide phosphodiesterase.